Attention-deficithyperactivity disorder (ADHD), is a neurobiological condition that causes hyperactivity, inattention, and impulsivity. The stimulant drug methylphenidate is often prescribed to people with this condition. It treats the symptoms. Scientists don’t fully understand the mechanism of the drug.
Researchers at the Okinawa Institute of Science and Technology Graduate University now know how certain brain areas respond to methylphenidate. Researchers may be able to identify the exact mechanism behind the drug and develop targeted treatments for the condition.
Research has shown that people with ADHD respond differently to rewards and anticipation than those without it. OIST scientists have suggested that ADHD patients release less dopamine, a neurotransmitter that is involved in reward-motivated behavior. Dopamine neurons fire more when a reward has been given.
In practice, this means that ADHD children and young adults may have trouble engaging in behavior that doesn’t lead to a positive outcome. Children may have difficulty focusing on schoolwork because it may not be rewarding at that time, even though it could lead to higher grades. Instead, they are distracted by external stimuli that seem novel and interesting, like a classmate talking or traffic sounds,” said Dr Emi furukawa, first author of the study, and a researcher at the OIST Human Developmental Neurobiology Unit. Professor Gail Tripp is the lead researcher.
Scientists believe that methylphenidate can help people with ADHD focus by increasing dopamine levels in the brain. Dr Furukawa and her team set out to study how the drug affects the ventralstriatum brain region, which is an important component of the reward system, and where dopamine is most abundantly released.
Furukawa stated, “We wanted to see how methylphenidate affects ventral striatum’s responses to reward cues. And delivery.”
The study was published in Neuropharmacology. This collaboration allowed the researchers access to IDOR’s functional electromagnetic resonance imaging (fMRI), facility, and allowed them to bring together expertise from different disciplines.
The brain is what you see
The researchers used fMRI (fMRI) to measure brain activity of young adults with ADHD. They played a computer game resembling a slot machine. Researchers scanned the ADHD group twice: once when they took medication methylphenidate, and again when they took a placebo. Each time the reels of the slot machine spun, the computer also showed one of two cues, either the Japanese character み (mi) or そ (so). While familiarizing themselves with the game before being scanned, the participants quickly learned that when the slot machine showed み, they often won money, but when the slot machine showed そ, they didn’t. The symbol み therefore acted as a reward-predicting cue, whereas そ acted as a non-reward-predicting cue.
The researchers found that the reward predicting cues and non-reward prediction cues triggered similar neuronal activity in the ventralstriatum of ADHD patients who took the placebo. The researchers found that methylphenidate increased activity in the ventralstriatum only in response to the reward cue. This indicated that they could now distinguish between the two cues more easily.
Researchers also looked at how neuronal activity within the striatum was correlated with neuronal activities in the medial prefrontal cortex — a brain region that is involved in decision-making and receives information from the external world and communicates with many brain regions, including thestriatum.
The participants with ADHD received money from the slot machine when they took placebo instead of methylphenidate. This was because neuronal activity in their striatum strongly correlated with activity in their prefrontal cortex at exactly the moment the reward was given. Researchers believe that people with ADHD communicate more actively with the prefrontal cortex and striatum, which could explain their increased sensitivity to external stimuli. This correlation was lower in participants who took methylphenidate than it was for people without ADHD.
These results suggest that methylphenidate’s therapeutic effects are due to a second neurotransmitter called norepinephrine. A subset of neurons in the prefrontal cortex releases norepinephrine. Researchers believe that methylphenidate could increase norepinephrine levels in the prefrontal cortex. This in turn regulates dopamine firing within the striatum, when rewards are delivered.
Furukawa stated, “It’s becoming obvious to us that methylphenidate modulates reward response is very complicated.”
Customizing ADHD Treatments
The scientists believe that further research can help to understand the mechanism of action of Methylphenidate. This could be of benefit to millions of people worldwide, despite the complexity.
Furukawa said that understanding the mechanism of methylphenidate could help scientists develop better ADHD treatments. She explained, “Methylphenidate can be effective, but there are side effects so some people are hesitant or unable to take it.” “If we can identify the part of the mechanism that produces therapeutic effects, we might be able to develop drugs with more targeted effects.”
Furukawa also hopes to understand how methylphenidate can affect the brain and provide behavioral interventions. Parents and teachers could help ADHD children stay focused by praising them often and reducing distracting stimuli.